The purpose of this research project is to determine the role of activated Protein C in the process of hemostasis. This will involve the purification and characterization of a co-factor for bovine activated Protein C which preliminary experiments indicate exists in blood. Secondly, the effect of the co-factor on the activated Protein C-catalyzed proteolysis of Factor Va and alpha-2-plasmin inhibitor will be evaluated. The effect of the co-factor on both the rates and extent of proteolysis will be studied. The effects on purified systems will be compared with those seen in plasma in order to evaluate the significance of each reaction. The second objective of the research will be to determine the physiological pathway for the activation of Protein C. A radioimmune assay for the activation peptide will be developed to monitor the activation of Protein C in plasma so that the degree of Protein C activation by various activators can be determined. Secondly, the kinetics of Protein C activation by thrombin will be evaluated in order to determine if thrombin can be the activator. By determining the degree of Protein C activation it will be possible to evaluate the significance of in vitro effects of activated Protein C.